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Four patients with clinically and genetically confirmed Prader-Willi syndrome (PWS) underwent nocturnal polysomnograpy (PSG), multiple sleep latency test (MSLT), human leukocyte antigens (HLA) typing and estimation of cerebrospinal fluid (CSF) hypocretin-1 (Hcrt-1) level to investigate if a role of hypothalamic dysfunction and sleep disturbance might be functionally connected through the hypocretin (orexin) system. In all four patients physical examination confirmed extreme obesity (increasing with age) with dysmorphogenetic features. Excessive daytime sleepiness (EDS) was manifested in only two subjects without any imperative feature. None of the patients under study suffered from cataplexy. Nocturnal PSG revealed fragmented sleep with low efficiency, the hypopnea and apnea indexes increasing from borderline up to very high values in direct proportion to the patients' age. MSLT latency was shortened in two patients with clinically expressed EDS, only one sleep onset rapid eye movements (REM) period (SOREM) was found. HLA typing showed DQB1*0602 positivity in two patients; the further two were negative. Mean value of CSF Hcrt-1 in the patients group was down to 164 +/- 46.8 pg/ml (in comparison with 265.8 +/- 48.8 pg/ml in 10 young healthy subjects, P=0.02). The deficiency of CSF Hcrt-1 level correlated in PWS patients with their EDS severity.

Blood specimens were collected from 15000 pregnant women during the first 3 months of their pregnancy and screened for amino acid disturbances by means of paper chromatography. A high incidence of disturbances in the phenylalanine metabolism was discovered: three cases of mild hyperphenylalaninaemia without phenylpyruvicaciduria (incidence 1:5000); two cases of mild hyperphenylalaninaemia with phenylpyruvicaciduria (incidence 1:7550); four cases of mild phenylketonuria (incidence 1:3750). Disturbances in the metabolism of other amino acids were found to be rare. Metabolic and genealogical findings in some detected families are briefly described.