Björn Hoffmann

Impact of longitudinal plasma leucine levels on the intellectual outcome in patients with classic MSUD.

Maple syrup urine disease (MSUD) is an inherited deficiency of branched chain α-ketoacid dehydrogenase (BCKDH) activity impairing the degradation of the branched chain amino acids valine, leucine, and isoleucine. Classic MSUD may lead to severe neonatal encephalopathy including coma and impaired cognitive outcome in later life. Early start of dietary treatment and careful metabolic control may improve the outcome of patients with classic MSUD. The aim of this study was to investigate the impact of long-term metabolic control assessed by plasma leucine levels on cognitive outcome in patients with classic MSUD. Plasma leucine levels of 24 patients were obtained retrospectively for the first 6 y of life and yearly medians of mean plasma leucine levels were calculated. At the age of 6 y, IQ tests were performed. Yearly medians of mean plasma leucine levels yielded three homogeneous clusters (low, intermediate, high). Patients of the low cluster showed statistically significant higher IQ scores compared with those of those of intermediate and high clusters. Long-term plasma leucine levels are associated with impaired cognitive outcome in patients with classic MSUD. To achieve the best possible intellectual outcome for affected individuals, we recommend that in infants and preschool children the target range for plasma leucine should not exceed 200 μmol/L.

Longitudinal assessment of intellectual achievement in patients with classical galactosemia.

OBJECTIVE: To conduct a longitudinal assessment of long-term cognitive outcome in patients with classical galactosemia. METHODS: Inclusion criteria were (1) previous assessment of IQ dating back >10 years with tests being comparable with the recent German tests HAWIK-III and HAWIE-R, (2) absence of illnesses other than galactosemia, (3) absence of foreign language problems, (4) enzymatic-metabolic proof of classical galactosemia, (5) compliance with dietary therapy, and (6) written informed consent. Twenty-three patients who fulfilled these criteria were found. They underwent the first IQ test at a mean age of 11 ± 5 years and the second 13.6 to 15.5 years later at a mean age of 26 ± 5 years. Results were corrected for the obsolescence of test norms (Flynn effect). RESULTS: Mean total IQ scores on the first and second tests were 78 ± 14 and 73 ± 15, respectively, and not significantly different. IQ scores in the average range were observed for 7 patients on the first test and for 5 patients on the second test. For 17 patients, the intraindividual IQ scores remained essentially unchanged. Five patients showed a decrease and 1 an increase of the IQ score over time. No consistent pattern of change was found with respect to performance or verbal IQ subscores or in achievements in the individual subtest. CONCLUSIONS: The results confirm the presence of reduced cognitive ability in classical galactosemia and present evidence for an absence of substantial galactosemia-induced aggravation of this impairment with increasing age, at least in patients from 4 to 40 years of age. It remains to be clarified whether a reduction of cognitive function in galactosemia may be initiated by an in utero toxicity of endogenously formed galactose and which role such a process may play in the development of intellectual deficiencies that are later maintained throughout life.

Fabry Disease—Often Seen, Rarely Diagnosed

BACKGROUND Data obtained from screened newborns and from persons at known risk for Fabry disease suggest that this condition is much more common in Germany than previously assumed. Its clinical manifestations are very diverse, and its differential diagnosis is correspondingly broad. Thus, there is often a delay before the diagnosis of Fabry disease is established. METHODS Selective literature search with special attention to studies of large groups of patients with respect to clinical manifestations, diagnostic evaluation, and treatment. RESULTS The number of patients carrying the diagnosis of Fabry disease in Germany lies far below what would be expected from published prevalence figures from other countries. Angiokeratoma, acroparesthesia, hypertrophic cardiomyopathy, impaired sweating and corneal opacification (cornea verticillata) are typical manifestations of Fabry disease; many patients also have other, nonspecific complaints, such as gastrointestinal disturbances. It has been clearly shown that women can manifest the entire range of clinical manifestations. Studies involving large groups of patients have improved our understanding of hearing impairment and tinnitus in Fabry disease. Therapeutic trials are currently in progress to determine whether enzyme substitution can delay the occurrence of life-threatening sequelae such as progressive renal failure and cerebrovascular events. CONCLUSIONS Fabry disease is still underdiagnosed. The average delay from the onset of symptoms to diagnosis is more than a decade. Treatment with human alpha-galactosidase A produced with genetic technology can improve most of the diseases manifestations.

Gastrointestinal symptoms in Fabry disease: everything is possible, including treatment.

Gastrointestinal symptoms in Fabry disease were first described independently by William Anderson and Johannes Fabry. Case reports and case series suggest that the whole gastrointestinal tract may be affected in patients with Fabry disease. The Fabry Outcome Survey (FOS) database supports these observations. The overall prevalence of gastrointestinal involvement reported in a study of 342 patients (271 adults; 71 children) enrolled in FOS was 52% (49.8% in adults, 60.8% in children). Abdominal pain was the most prevalent symptom. The median age at onset of gastrointestinal symptoms was 14 years, similar to the age at onset of acroparaesthesia. The prevalence of gastrointestinal symptoms was reduced in patients after receiving enzyme replacement therapy with agalsidase alfa for 12 and 24 months. There was no correlation between gastrointestinal symptoms and body mass index.

Zur Behandlungssituation erwachsener Patienten mit angeborenen Stoffwechselkrankheiten

ZusammenfassungHintergrund und Ziel:Fortschritte in der Diagnostik und Therapie angeborener Stoffwechselkrankheiten haben zur Verbesserung von Prognose und Outcome der Patienten geführt. Viele dieser Patienten haben inzwischen das Erwachsenenalter erreicht und sollten durch Internisten oder Allgemeinmediziner behandelt werden. In dieser Studie wurde die Behandlungssituation erwachsener Patienten mit Stoffwechselkrankheiten in Deutschland untersucht.Methodik:26 Kinderkliniken, die schwerpunktmäßig u. a. Patienten mit Stoffwechselkrankheiten behandeln, erhielten einen Fragebogen, bestehend aus 14 Fragen.Ergebnisse:16/26 Kliniken schickten den Fragebogen zurück. Nur eine Klinik hat eine eigene internistische Sprechstunde für erwachsene Patienten mit Stoffwechselkrankheiten. Zwei weitere Medizinische Kliniken kooperieren mit Kinderkliniken. Ein großer Teil der antwortenden Kinderkliniken gestand Probleme in der Betreuung erwachsener Patienten mit Stoffwechselstörungen ein.Schlussfolgerung:Erwachsene Patienten mit Stoffwechselstörungen werden zum großen Teil durch Kinderärzte betreut. Es müssen dringend Strukturen zur adäquaten und suffizienten Betreuung dieser wachsenden Patientengruppe geschaffen werden.AbstractBackground and Purpose:Advances in diagnosis and therapy of inborn errors of metabolism have improved prognosis and outcome of affected patients. Many patients have reached adulthood already, and thus may be attended by adult physicians. In this study the authors evaluated the situation of adult patients with metabolic diseases in Germany.Methods:26 pediatric departments with a special metabolic unit were asked to answer a questionnaire of 14 questions.Results:16/26 departments completed the questionnaire. Only one hospital maintains an outpatient department for adult patients with metabolic diseases. Two additional internal medical departments collaborate with a pediatric metabolic center. Many of the answering pediatric departments conceded problems in the treatment of adult patients with metabolic diseases.Conclusion:Adults with inborn errors of metabolism are mostly attended by pediatricians, also beyond adolescence. There is an urgent need for structures that guarantee appropriate and sufficient treatment of this continuously growing population.

Situation of adult patients with inborn errors of metabolism. A survey in Germany

ZusammenfassungHintergrund und Ziel:Fortschritte in der Diagnostik und Therapie angeborener Stoffwechselkrankheiten haben zur Verbesserung von Prognose und Outcome der Patienten geführt. Viele dieser Patienten haben inzwischen das Erwachsenenalter erreicht und sollten durch Internisten oder Allgemeinmediziner behandelt werden. In dieser Studie wurde die Behandlungssituation erwachsener Patienten mit Stoffwechselkrankheiten in Deutschland untersucht.Methodik:26 Kinderkliniken, die schwerpunktmäßig u. a. Patienten mit Stoffwechselkrankheiten behandeln, erhielten einen Fragebogen, bestehend aus 14 Fragen.Ergebnisse:16/26 Kliniken schickten den Fragebogen zurück. Nur eine Klinik hat eine eigene internistische Sprechstunde für erwachsene Patienten mit Stoffwechselkrankheiten. Zwei weitere Medizinische Kliniken kooperieren mit Kinderkliniken. Ein großer Teil der antwortenden Kinderkliniken gestand Probleme in der Betreuung erwachsener Patienten mit Stoffwechselstörungen ein.Schlussfolgerung:Erwachsene Patienten mit Stoffwechselstörungen werden zum großen Teil durch Kinderärzte betreut. Es müssen dringend Strukturen zur adäquaten und suffizienten Betreuung dieser wachsenden Patientengruppe geschaffen werden.AbstractBackground and Purpose:Advances in diagnosis and therapy of inborn errors of metabolism have improved prognosis and outcome of affected patients. Many patients have reached adulthood already, and thus may be attended by adult physicians. In this study the authors evaluated the situation of adult patients with metabolic diseases in Germany.Methods:26 pediatric departments with a special metabolic unit were asked to answer a questionnaire of 14 questions.Results:16/26 departments completed the questionnaire. Only one hospital maintains an outpatient department for adult patients with metabolic diseases. Two additional internal medical departments collaborate with a pediatric metabolic center. Many of the answering pediatric departments conceded problems in the treatment of adult patients with metabolic diseases.Conclusion:Adults with inborn errors of metabolism are mostly attended by pediatricians, also beyond adolescence. There is an urgent need for structures that guarantee appropriate and sufficient treatment of this continuously growing population.

Zur Behandlungssituation erwachsener Patienten mit angeborenen Stoffwechselkrankheiten@@@Situation of Adult Patients with Inborn Errors of Metabolism. A Survey in Germany: Eine Erhebung in Deutschland

ZusammenfassungHintergrund und Ziel:Fortschritte in der Diagnostik und Therapie angeborener Stoffwechselkrankheiten haben zur Verbesserung von Prognose und Outcome der Patienten geführt. Viele dieser Patienten haben inzwischen das Erwachsenenalter erreicht und sollten durch Internisten oder Allgemeinmediziner behandelt werden. In dieser Studie wurde die Behandlungssituation erwachsener Patienten mit Stoffwechselkrankheiten in Deutschland untersucht.Methodik:26 Kinderkliniken, die schwerpunktmäßig u. a. Patienten mit Stoffwechselkrankheiten behandeln, erhielten einen Fragebogen, bestehend aus 14 Fragen.Ergebnisse:16/26 Kliniken schickten den Fragebogen zurück. Nur eine Klinik hat eine eigene internistische Sprechstunde für erwachsene Patienten mit Stoffwechselkrankheiten. Zwei weitere Medizinische Kliniken kooperieren mit Kinderkliniken. Ein großer Teil der antwortenden Kinderkliniken gestand Probleme in der Betreuung erwachsener Patienten mit Stoffwechselstörungen ein.Schlussfolgerung:Erwachsene Patienten mit Stoffwechselstörungen werden zum großen Teil durch Kinderärzte betreut. Es müssen dringend Strukturen zur adäquaten und suffizienten Betreuung dieser wachsenden Patientengruppe geschaffen werden.AbstractBackground and Purpose:Advances in diagnosis and therapy of inborn errors of metabolism have improved prognosis and outcome of affected patients. Many patients have reached adulthood already, and thus may be attended by adult physicians. In this study the authors evaluated the situation of adult patients with metabolic diseases in Germany.Methods:26 pediatric departments with a special metabolic unit were asked to answer a questionnaire of 14 questions.Results:16/26 departments completed the questionnaire. Only one hospital maintains an outpatient department for adult patients with metabolic diseases. Two additional internal medical departments collaborate with a pediatric metabolic center. Many of the answering pediatric departments conceded problems in the treatment of adult patients with metabolic diseases.Conclusion:Adults with inborn errors of metabolism are mostly attended by pediatricians, also beyond adolescence. There is an urgent need for structures that guarantee appropriate and sufficient treatment of this continuously growing population.