Also clinically heterogeneous but urinary organic acid and plasma carnitine and acylcarnitine studies will prompt this evaluation

Clinically heterogeneous, including neonatal hypotonia and epileptic seizures, Leigh and Leigh-like syndromes, episodic ataxia and paroxysmal dystonia. Lactates may be normal Basal ganglia abnormality (especially globus pallidus) may be a clue.

The storage of cultured fibroblasts, like the retention of DNA samples, is one of the prerequisites for later genetic diagnosis of unexplained disorders. Some types of fibroblast study are particularly important

Golgi and endoplasmic reticulum disorders (congenital defects of glycosylation) Attaching sugar molecules to proteins or lipids (glycosylation) is mediated by the Golgi apparatus or complex and by the endoplastic reticulum and is necessary for numerous biochemical functions. Defects may be divided into soluble and structural abnormalities. The 'soluble' congenital defects of glycosylation (CDG) - predominantly defects of N-glycosylation - are many and increasing in number but by far the most important is CDG1a. 'structural' defects of O-glycosylation comprise congenital and later onset muscular dystrophies and are investigated by completely different...

  Peroxisomes are spherical 1pm diameter organelles with a multitude of oxidative and other enzymes packed within a single-layered membrane (http://www.peroxisomedb. org) global' peroxisomal disorders with impaired peroxisomal biogenesis (fewer or even no peroxisomes), together with those single peroxisomal enzyme defects that induce a similar phenotype (in particular, D-bifunctional protein deficiency) adrenoleukodystrophy, due to an X-linked defect of the peroxisomal ABCD1 gene that codes for the peroxisomal membrane protein ABCD1, a member of the ATP-hmding cassette transporters. While estimation of very...

Mitochondrial disorders With the explosion of knowledge about disorders of the mitochondria, definitive investigations have become more complex and specialized. However, clinical clues can point towards a mitochondrial disorder and fairly simple tests support the diagnosis sufficiently to proceed to specific investigations of mitochondrial function. To a certain extent there is a relationship between the type of disease and the site of metabolic defect along the pathway from the inner mitochondrial membrane to the termination of the respiratory chain, but there is considerable heterogeneity. It has long been known that most of the...

Lysosomal enzyme deficiencies may be sought in serum or plasma, in leukocytes (white cell pellet) or in cultured fibroblasts. Although it is evident that there is great variation in the severity of the neurological disorders which may result from a severe lysosomal enzyme deficiency, extreme caution is necessary when partial deficiency is found, particularly 'within the heterozygous range', since in some of these disorders the prevalence of heterozygosity is quite high in the normal population. The term 'pseudodeficiency' is used in lysosomal storage diseases to denote the situation in which individuals show greatly...