Evelina Maines

Lysinuric protein intolerance can be misdiagnosed as food protein–induced enterocolitis syndrome

To the Editor, Food protein–induced enterocolitis syndrome (FPIES) is a rising non-IgE-mediated food allergy triggered by specific food proteins (cow’s milk, soy, and grains are the common offending foods). FPIES requires total elimination of the offending food from the diet and typically resolves by 3 yr of age (1). Metabolic disorders, such as lysinuric protein intolerance (LPI), are often underestimated in the differential diagnosis of FPIES. Although rare, these inherited conditions require different and life-long nutrition and dietary intervention to prevent impaired developments in infants. We present the case of an infant with LPI misdiagnosed as FPIES and discuss the similarities and differences between these two conditions. A 12-month-old male infant, exclusively breastfed for the first 6 months of life, was admitted due to repetitive vomiting and diarrhea, commenced at 6 months after weaning began. These reactions typically occurred within 1–3 h after the consumption of the same foods–meat, chicken, fish, or eggs. None of these reactions were associated with bloody diarrhea, skin rash, angioedema, or dyspnea. Prior to our examination, the parents gradually eliminated these foods from his diet and reported an improvement in symptoms. The infant clinical and neurologic examinations were normal. A mild hepatosplenomegaly was revealed by an abdominal ultrasonography. Thyroid-stimulating hormone, free thyroxine, celiac serology, blood gases, ammonia, renal and liver functions, and urinalysis were all in the normal range. Only ferritin and LDH serum levels were very high (244 ng/ml and 1017 IU/l, respectively). A complete allergological work-up was performed, which came out negative for skin prick tests, patch tests, and serum-specific IgE antibodies to the suspected foods (total IgE < 2 kU/l). A FPIES to solid food was diagnosed. Due to the history of aversion to protein-rich foods associated with mild hepatosplenomegaly and very high ferritin and LDH serum levels, plasma and urinary amino acid analysis were carried out. The results showed in Table 1 led to a definitive diagnosis of LPI, which was confirmed by the molecular analysis of SLC7A7 gene (the patient was a homozygote with a missense mutation c. 1001T > G in SLC7A7 gene; his parents resulted heterozygous carriers of this mutation). The child started a low-protein diet (1.5 g/Kg/day) and oral supplementation with citrulline (100 mg/kg/day), reporting no further gastrointestinal or neurologic symptoms after 6 months of good compliance with this therapy. Lysinuric protein intolerance is a rare autosomal recessive defect of cationic amino acid (i.e. lysine, arginine, and ornithine) transport at the basolateral membrane of epithelial cells in intestine and kidney, which results in low activity of the urea cycle and possible episodes of hyperammonemia, particularly after ingesting protein-rich foods. The condition is caused by mutations in SLC7A7 gene (2, 3). Patients with LPI are usually asymptomatic while breast-feeding, but typically develop recurrent emesis and diarrhea during weaning, a few hours after being fed protein-rich foods. However, LPI can have a wide variability in its clinical manifestations, which range from aversion to protein-rich foods, failure to thrive and hepatosplenomegaly, to renal insufficiency, pulmonary alveolar proteinosis, and hematologic and immunologic abnormalities (4).

Serum inhibin B levels before and after varicocelectomy in early adolescence

Background: Whereas no clear relationship has been observed between varicocelectomy and serum inhibin B levels in men, in adolescents comparison between inhibin B levels before and after varicocelectomy is lacking. Aim: To evaluate the effect of varicocele surgical treatment on inhibin B levels in adolescents at the beginning of puberty compared to a group of healthy adolescents. Subjects and methods: We studied 28 adolescents in Tanner 2 pubertal stage with a grade III left-sided varicocele (patients) compared to 13 age- and pubertal stage-matched healthy adolescents (controls). All patients underwent blood tests to determine serum inhibin B levels before and 6 months after varicocelectomy by Palomo procedure. For comparison we investigated inhibin B levels in controls and repeated this test 6 months later. Testicular ultrasound was performed for patients only. Results: Baseline inhibin B concentrations of patients and controls were 109.90±40.26 and 109.33±38.34 pg/ml, respectively. No significant changes were observed in patients’ inhibin B concentrations after varicocelectomy (116.00±42.65 pg/ml), or in controls during the 6 months’ follow-up (99.12±30.09 pg/ml). Doppler examination after treatment shows a complete resolution of varicocele in all the patients without alterations in testicular parenchyma. Conclusions: Varicocelectomy performed on adolescents at T2 pubertal stage might be useful to avoid alteration in inhibin B production and consequently in testicular function. Further studies are necessary to confirm the prognostic value of inhibin B levels and the benefit of early varicocelectomy in preserving the fertility of these adolescents.

Type III Bartter-like syndrome in an infant boy with Gitelman syndrome and autosomal dominant familial neurohypophyseal diabetes insipidus.

Abstract We report the case of an infant boy with polyuria and a familial history of central diabetes insipidus. Laboratory blood tests disclosed hypokalemia, metabolic alkalosis, hyperreninemia, and hyperaldosteronism. Plasma magnesium concentration was slightly low. Urine analysis showed hypercalciuria, hyposthenuria, and high excretion of potassium. Such findings oriented toward type III Bartter syndrome (BSIII). Direct sequencing of the CLCNKB gene revealed no disease-causing mutations. The water deprivation test was positive. Magnetic resonance imaging showed a lack of posterior pituitary hyperintensity. Finally, direct sequencing of the AVP-NPII gene showed a point mutation (c.1884G>A) in a heterozygous state, confirming an autosomal dominant familial neurohypophyseal diabetes insipidus (adFNDI). This condition did not explain the patient’s phenotype; thus, we investigated for Gitelman syndrome (GS). A direct sequencing of the SLC12A3 gene showed c.269A>C and c.1205C>A new mutations. In conclusion, the patient had a genetic combination of GS and adFNDI with a BSIII-like phenotype.

Genotype in the diagnosis of 21-hydroxylase deficiency: Who should undergo CYP21A2 analysis?

Aims: to confirm the diagnosis of 21-hydroxylase deficiency (21-OHD) by the analysis of CYP21A2 gene in infants with clinical and/or biochemical features of 21-OHD in order to clarify which patients to submit to genetic analysis; to analyze the genotype-phenotype concordance in these infants. Subjects and methods: We studied 25 children with clinical and/or biochemical features of 21-OHD. All of them and their parents were submitted to genetic analysis of CYP21A2. Patients were classified in 3 groups according to mutations’ severity: severe (group A), moderate (group B) or mild (group C). Results: CYP21A2 gene mutations were found in 17 children. Whereas all infants of groups A and B presented a classical form of 21-OHD, children of group C had a non-classical form of 21-OHD. Four infants resulted heterozygotes and 4 children were wild-type. A girl clinically presenting a non-classical form of 21-OHD resulted compound heterozygote with one of the mutations not described in literature (R25W) and whose residual enzymatic activity is not already known. All affected children presented a 17-OHP level after ACTH stimulation greater than 100 nmol/l. We found an optimal concordance between 17-OHP levels after ACTH test and genotype. Conclusions: CYP21A2 analysis permitted to confirm the diagnosis of 21-OHD in 68% of our children. To improve this percentage we suggest to perform the CYP21A2 analysis only when 17-OHP after ACTH test is greater than 100 nmol/l. Moreover, we found an optimal genotype-phenotype concordance in the 21-OHD patients.

Newborn with rhizomelia and difficulty breathing

1 Department of Pediatrics, Regional Centre for Newborn Screening, Diagnosis and Treatment of Inherited Metabolic Diseases and Congenital Endocrine Diseases, Azienda Ospedaliera Universitaria Integrata of Verona, Piazzale Ludovico Antonio Scuro, 10, 37134 Verona, Italy 2 Pediatric Clinic, Department of Life and Reproduction Sciences, University of Verona, Verona, Italy Skeletal Radiol (2017) 46:231 DOI 10.1007/s00256-016-2536-y

Images from 18F-DOPA Scan in Congenital Hyperinsulinism: Not Always a Clue for Diagnosis

Congenital hyperinsulinism (CHI) is the most common cause of persistent hypoglycaemia in childhood (Horm Res 70:65-72, 2008; J Clin Endocr Metab 93:869-875, 2008). 18−Fluoro-L-dihydroxy-phenylalanine (18F-DOPA) positron emission tomography (PET) can detect areas of increased activity in the pancreas and may differentiate focal from diffuse CHI (J Clin Endocr Metab 93:869-875, 2008; Radiology 253:216-222, 2009). We here report the case of a girl who complained of recurrent episodes of severe hypoglycaemia despite previous partial pancreatectomy. To evaluate the need for additional surgical intervention, we performed 18F-DOPA PET/computed tomography (CT), which showed a focal lesion corresponding to the anatomical region of the pancreatic tail. On the other hand, abdominal magnetic resonance imaging (MRI) clearly demonstrated that the 18F-DOPA uptake was in a loop of bowel occupying the previous surgical bed. Our case highlights that bowel uptake can be a possible pitfall in the interpretation of 18F-DOPA PET/CT in children affected by CHI, suggesting that when 18F-DOPA PET/CT results do not fit the clinical picture, magnetic resonance imaging (MRI) may allow a more accurate correlation of the radiotracer activity with the underlying anatomical or pathological structure.

A neonate with abdominal distension and failure to thrive

A full-term male was born after a pregnancy complicated between 22 and 31 weeks of gestation by non-immune hydrops fetalis (NIH). At 48 h of life, the physical examination revealed jaundice, which was treated successfully with conventional phototherapy for 24 h, and mild hepatomegaly, which was not promptly investigated. At 20 days of life, the patient presented with a clinical picture of failure to thrive and significant abdominal distension (figure 1). Liver and spleen were palpable at 7 and 8 cm below the costal margin, respectively. The patient was dystrophic without dysmorphic features or signs of neurological involvement. Liver enzyme levels and cholestasis indices were significantly altered (aspartate aminotransferase 126 U/L gamma glutamyl transferase 283 U/L, alkaline phosphatase 533 U/L, total bilirubin 58 mmol/L, conjugated bilirubin 41 mmol/L), while leucocyte count, haemoglobin level, coagulation parameters, albumin and serum glucose level were …

Painless bilateral swelling of the face: think about cherubism

A 4-year-old Caucasian male child was referred to our padiatric clinic with bilateral facial swelling. When he was 3 years old, he had started to develop an enlargement of the cervical lymph nodes and of the jaw, which gave him a full-faced cherubic appearance (figure 1). Clinical examination revealed swelling of both rami of the mandible with bilateral expansion of the mandibular angle extending to the molar and retromolar regions. Panoramic radiography showed generalised multicystic bilateral radiolucent lytic …

Bone density in children treated with gonadotropin-releasing hormone analogs for central precocious puberty

Estrogens, growth hormones and IGFs are essential in the development and growth of the skeleton and for the maintenance of bone mass and density. Treatment of precocious puberty with gonadotropin-releasing hormone analogs (GnRHa), leads to a situation of hypoestrogenism by reducing sex-steroid levels, which, theoretically, may have a detrimental effect on bone mass during pubertal development. A reduction in bone mineral density during GnRHa treatment has been shown, but GnRHa treatment in patients with central precocious puberty does not seem to impair the achievement of normal peak bone mass at adult height. However, calcium supplementation is effective in improving bone densitometric levels and may promote better peak bone mass achievement.