Liver failure and neurologic disease in a patient with homocystinuria.

A homocystinuric patient with the typical clinical and metabolic features of the disorder started treatment at 22 years of age. A diet with controlled methionine intake resulted in good metabolic control for five years, but control could not be attained for the following 1 1/2 years. This was accompanied by the development of paraparesis and increasing liver failure.

Cerebral glucose metabolism in adults with early treated classic phenylketonuria.

Classic phenylketonuria (PKU) is characterized by severe mental retardation in untreated individuals and mild neurocognitive abnormalities in some early treated adults. The exact biochemical mechanisms underlying this neurotoxicity remain undetermined. Several theories implicate abnormal cerebral energy utilization and alterations in biochemical pathways that involve glucose metabolism.

Paroxetine in the treatment of generalised anxiety disorder.

Paroxetine is a selective serotonin re-uptake inhibitor useful in the treatment of a wide range of psychiatric disorders. Generalised anxiety disorder (GAD) is characterised by excessive persistent anxiety and worry about a number of events and activities occurring on more days than not for at least 6 months. GAD is the most common anxiety disorder in primary care settings.

Maple syrup urine disease: identification and carrier-frequency determination of a novel founder mutation in the Ashkenazi Jewish population.

Maple syrup urine disease (MSUD) is a rare, autosomal recessive disorder of branched-chain amino acid metabolism. We noted that a large proportion (10 of 34) of families with MSUD that were followed in our clinic were of Ashkenazi Jewish (AJ) descent, leading us to search for a common mutation within this group. On the basis of genotyping data suggestive of a conserved haplotype at tightly linked markers on chromosome 6q14, the BCKDHB gene encoding the E1beta subunit was sequenced.

Influence of metabolic control on growth in homocystinuria due to cystathionine B-synthase deficiency.

The etiology of the tall stature almost invariably seen in homocystinuric patients is not known. The effect of metabolic control and the role of the GH-IGF system on growth were investigated in 10 patients with homocystinuria. There was a direct correlation between the plasma free homocyst(e)ine and growth velocity SD scores in 18 patient years (r, 0.

Successful pregnancy in severe methylmalonic acidaemia.

Methylmalonic acidaemia is an inborn error of metabolism characterized by recurrent episodes of life-threatening ketoacidosis. With improved and intensive treatment, these patients are living into adulthood, but many experience late-onset disease complications such as chronic renal failure, chronic pancreatitis and osteopenia. We report the successful delivery of a healthy baby to a 20-year-old woman with vitamin B12-unresponsive methylmalonic acidaemia who has these late-onset manifestations of the disease and had plasma methylmalonic acid concentrations of 1900 mumol/L during the first trimester of pregnancy.

Newborn screening for homocystinuria.

It is becoming increasingly apparent that pyridoxine responsive homocystinuria patients are being missed by newborn screening programs. The possibility that screening for homocystine, rather than the methionine, might be more effective was investigated by comparing homocystine and methionine levels of non-responsive patients at diagnosis. The plasma methionine levels of 11 infants were much more abnormal than the homocystine levels.

Molecular basis of phenotypic variation in patients with argininemia.

Argininemia is an autosomal recessive disorder caused by a deficiency in the liver-type arginase enzyme. Clinical manifestations include progressive spastic diplegia and mental retardation. While the quality of life can severely deteriorate in most such patients, some do show remarkable improvement in neurological symptoms while on controlled diets.

Baclofen in the treatment of polymyoclonus and ataxia in a patient with homocystinuria.

A patient with homocystinuria due to cystathionine beta-synthase deficiency developed severe progressive polymyoclonus and ataxia. To our knowledge, this is the first time polymyoclonus and ataxia have been reported in association with homocystinuria. Although cerebrovascular thrombosis is usually thought to be responsible for neurologic dysfunction in homocystinuric patients, no infarctions were demonstrated on magnetic resonance imaging scans in our case.

Comparison of phenylketonuric and nonphenylketonuric sibs from untreated pregnancies in a mother with phenylketonuria.

Two children, one with phenylketonuria (PKU) and the other nonphenylketonuric, from untreated pregnancies in a mother with PKU provided the opportunity to compare the degree of damage from maternal PKU between these genotypically different fetuses. Both the phenylketonuric offspring and her nonphenylketonuric sib were microcephalic at birth and had congenital anomalies, esophageal atresia in the former and congenital dislocation of the hip in the latter. However, the phenylketonuric child also had intrauterine growth retardation while the nonphenylketonuric sib had normal weight and length at birth.

Successful long term therapy of biopterin deficiency.

A hyperphenylalaninaemic infant, started on dietary therapy at 14 days of age, had severe developmental retardation and neurological abnormalities despite excellent biochemical control. A diagnosis of a deficit in biopterin synthesis was made at five months of age as a result of the following: high neopterin and low biopterin levels in both blood and urine, normal dihydropteridine reductase in the liver and a sharp drop in the plasma phenylalanine level 4 h after the administration of a test dose of tetrahydrobiopterin. Treatment with levodopa, carbidopa and 5-hydroxytryptophan resulted in prompt neurological improvement.

The relationship between the branched chain amino acids and their alpha-ketoacids in maple syrup urine disease.

Plasma branched chain amino acid levels and their respective ketoacid analogues were determined in seven maple syrup urine disease patients ranging in age from 12 h to 12 years. One hundred one pairs were analyzed. There was a high degree of correlation between the amino acid and its ketoacid analogue at every amino acid level.

Familial congenital short small bowel with associated defects. A long-term survival.

In 1974, Royer et al. described a familial syndrome consisting of a short and sluggish small bowel, malrotation of the gut, and pyloric stenosis. These authors stressed the uniformly fatal outcome of their four cases, as well as other possibly unrecognized cases previously described in the literature.

Disseminated ulcerations in allergic eosinophilic gastroenterocolitis.

An infant with allergic eosinophilic gastroenterocolitis is described. The patient presented with vomiting, diarrhea, gastrointestinal bleeding, and failure to thrive. Anemia, hypoproteinemia, and peripheral eosinophilia were also present.

Plasma and cerebrospinal fluid amino acid concentrations in phenylketonuria during the newborn period.

Plasma and cerebrospinal fluid amino acid values were determined in 29 infants 9 to 30 days of age with a confirmed diagnosis of phenylketonuria. Phenylalanine concentrations in plasma and cerebrospinal fluid were markedly elevated; the degree of elevation in the cerebrospinal fluid had a significant relationship to that of the plasma. The only other significant deviations in the plasma were reductions in the threonine and tyrosine values.

An immunodeficient child with inflammatory bowel disease: involvement of cyclic nucleotides and effects of lithium.

A 3-year-old male with inflammatory bowel disease and hypogammaglobulinemia was found to have decreased T lymphocyte function. His serum was shown to depress normal T cell proliferative responses to phytohemagglutinin. Incorporation of lithium chloride to in vitro cultures enhanced autologous lymphocyte responses to phytohemagglutinin.