David M. Danks

Cerebro-hepato-renal syndrome of Zellweger. A report of eight cases with comments upon the incidence, the liver lesion, and a fault in pipecolic acid metabolism.

Studies of eight patients with this syndrome confirm the characteristic pattern of abnormalities and the autosomal recessive mode of inheritance. The incidence is estimated to be approximately 1 in 100,000 live births. The liver lesion proved to be variable, with features of progressive parenchymal damage rather than a developmental defect of small bile ducts as previously suggested. Elevated levels of pipecolic acid were found in blood and urine and may be related to the basic defect.

Chondrodysplasia punctata—23 cases of a mild and relatively common variety

A common form of chondrodysplasia punctata has been defined by characteristic clinical and radiologic features in 23 patients seen in Melbourne. The patients presented during infancy because of failure to thrive, apparent mental retardation, and/or unusual appearance. The typical facies is almost diagnostic, and the diagnosis is completed by finding punctate calcification in the calcaneum in lateral radiographs of the feet, and sometimes in other sites. Growth and developmental progress improved during childhood and the final outcome seems likely to comprise low normal height and intelligence with persistence of typical facies. Mild cases probably pass unrecognized at present. Seventeen patients were male. Paternal age was significantly increased; however, family data did not support a genetic cause. Illnesses during pregnancy were unusually frequent, and anticonvulsants taken during pregnancy may have had an etiologic role in some patients.

Iminopeptiduria, skin ulcerations, and edema in a boy with prolidase deficiency

A 12-year-old boy with recurrent skin ulceration, chronic generalized lymphedema, and mild mental retardation was found to excrete massive amounts of dipeptides, most (but not all) of which had proline or hydroxyproline as the carboxyl terminal residue. Glycylproline predominated. Prolidase deficiency was demonstrated in red blood cells and in fibroblastic cells. Prolidase activity was present in continuous lymphoid cell cultures at the same low level observed in control cells.

A mild form of Menkes steely hair syndrome

careful monitoring of all urine collections in the hospital; absolute certainty of the blood cell source was based on minor blood group typing of the red cells in the urine. Minor blood group typing is particularly valuable when patients and their parents are of the same major blood group type. We suggest that this technique is preferable to the use of chromium 5 I-labeled erythrocytes in children when a factitious etiology of bleeding is suspected because of reduced radioactivity exposure, and because of the general availability of minor blood group typing techniques. The attentiveness and cooperation of all physicians and nurses is critical because parents frequently seek discharge for their child when suspicion by staff members develops? .3 Consideration of factitious hematuria in the differential diagnosis of hematuria may obviate painful and potentially harmful investigations as well as unnecessary courses of medications.

Nonketotic hyperglycinemia: Analyses of glycine cleavage system in typical and atypical cases

The molecular nature of the glycine cleavage system was investigated in eight patients with typical (neonatal) and two patients with atypical (late onset) nonketotic hyperglycinemia (NKH). The overall activity of the glycine cleavage system was found to be decreased in all of the liver and brain tissue studied, but it was undetectable or extremely low in typical NKH, whereas there was some residual activity in atypical NKH. Six patients with typical NKH had a specific defect in the P protein, and one a defect in the T protein; the activity of the T protein was defective in one patient with atypical NKH.

Hypohidrotic ectodermal dysplasia: A study of sweat pores in the X-linked form and in a family with probable autosomal recessive inheritance

Three families containing patients with X-linked hyoohidrotic ectodermal dysplasia have been studied by a simple technique which provides a permanent impression of the fingertip suitable for microscopic examination and counting of the sweat pores. No sweat pores were found in affected males. A diminished sweat pore count was found in only 1 of 5 heterozygous females. In one family a boy and girl were found to have a form of hypohidrotic ectodermal dysplasia in which sweat pores are reduced in number but not absent. Autosomal recessive inheritance seems probable in this form.

The use of restriction fragment length polymorphisms in prenatal diagnosis of dihydropteridine reductase deficiency.

Using a human dihydropteridine reductase (hDHPR) cDNA probe we have detected two AvaII and one MspI restriction fragment length polymorphisms (RFLPs). We show that these RFLPs are in disequilibrium and calculate that approximately 60% of Caucasians are heterozygous for at least one RFLP. We demonstrate the usefulness of these RFLPs in prenatal diagnosis of DHPR deficiency in one family. This disorder can also be predicted by enzyme assays and we therefore discuss the relative merits of the two methods of prenatal diagnosis.

Comments upon the classification of infantile polycystic diseases of the liver and kidney, based upon three-dimensional reconstruction of the liver

Three-dimensional reconstructions of portal tracts of two babies with different forms of infantile polycystic disease of the kidney and liver, and of a child with congenital hepatic fibrosis, have shown important differences between these three conditions. A strong plea is made for the application of this technique, and of microdissection of kidneys, to a large series of cases in order to develop a valid classification of these conditions.

Demonstration of two forms of phenylalanine hydroxylase in human liver obtained at autopsy

Abstract 1. 1. Phenylalanine hydroxylase ( l -phenylalanine tetrahydropteridine: O2 oxidoreductase (4-hydroxylating), EC 1.14.3.1) has been demonstrated to be present in human liver obtained at autopsy. 2. 2. The enzyme is shown to be present in 2 forms: (a) a ‘soluble’ form, which remains in the 6000 × g supernatant; (b) a ‘particulate’ form which sediments at 6000 × g. 3. 3. The particulate form has been solubilised and its properties suggest that it is bound to a membrane via a lipid linkage. 4. 4. Some properties of the two forms have been studied and these suggest that they are closely related. 5. 5. It should now be possible to use human livers obtained at autopsy as a source of phenylalanine hydroxylase for purification and study.

Phenylalanine hydroxylase activity in human foetal fibroblastic cells in culture.

Abstract 1. 1. A thorough investigation of cultured fibroblastic cells (foetal and adult) for phenylalanine hydroxylase activity is being undertaken. Absence of this tissue-specific enzyme from cultured cells has been generally assumed, but no study of normal fibroblastic cells has been published. Another tissue-specific enzyme (cystathionine synthetase) has recently been found in adult cultured fibroblasts by other workers. 2. 2. Foetal cells were studied first, and substantial amounts of activity were found in fibroblastic cells cultured from muscle, but not in fresh homogenates of foetal muscle. 3. 3. Enzyme activity persisted throughout many subcultures, but showed marked daily variation within any one subculture. The cause of this variation has not yet been identified. 4. 4. Studies of the basic defect in phenylketonuria will be aided greatly if phenylalanine hydroxylase activity can be demonstrated in cultured fibroblasts obtained post-natally. Preliminary studies of adult cells have been disappointing, but optimal conditions have probably not been achieved.