*2.1. Study Design and Participants*

At our Regional Referral Centre for Metabolic diseases, Pediatric Clinic, Department of Clinical and Experimental Medicine, patients with different types of IEM are followed. At the time of the study, 33 of them were affected by a treatable LSD and thus were regularly admitted to the Day Hospital with a personal schedule of ERT (weekly or every other week) or followed-up every 3–6 months because of treatment at home.

In this study, we included 15/33 patients who accepted to undergo our interview. There were 9 females and 6 males with age ranging from 3 to 40 years. Seven of them were younger than 12 years.

Ten (66%) had Pompe disease (PD; 2 early infantile type (EOPD) and 8 late-onset type (LOPD)). The sample also included 2 patients with Mucopolysaccharidosis type IV (MPS IV), 2 pediatric patients with Gaucher disease, and 1 adult subject with Fabry disease. All participants were receiving iv ERT (alglucosidase alfa, elosulfase alfa, imiglucerase, or agalsidase beta, according to their disease). At the beginning of COVID-19 emergency, study patients with Gaucher disease or Fabry disease were on home therapy.

An ad hoc structured interview was developed and administered by phone and when possible by video calls (Table 1) during the third week of lockdown. The interview investigated personal feelings, familial relationship, degree of faith in others, and future perspectives and was inspired and developed in light of this extraordinary, life-threatening event. Quantitative data were obtained from dichotomous questions (Yes/No) used for a clear distinction of respondents' opinions.

According to the age, we got direct information from 8 subjects, while for 7 pediatric patients, the parents were asked to respond to the interview. A psychologist (GL) from the Centre contacted the patients or their caregivers to assess how the COVID-19 emergency modified the daily life of patients and their family, which changes were due to the resulting Government restrictions, how these were felt, and if any change had occurred with the personal therapy schedule. Moreover, we gathered information about the mood of the patients, their families, and social relationships, the need for psychological support, and their expectations for the future. Since we thought and developed the interview in light of this extraordinary event, the tool could not have been previously validated. To overcome this issue, a group of healthy volunteers was carefully selected for comparison. The control group included 15 healthy subjects matching one-to-one with the patient and caregiver sample, in terms of age, social condition, instruction level, and family composition.

#### **Table 1.** Structured interview (topic guide).


#### *2.2. Statistical Analyses*

Data were presented as absolute frequencies and/or percentages for categorical variables. A comparison of proportions between groups was conducted by Chi square test with Yates' correction. Differences with *p* ≤ 0.05 were considered to be significant. Data were analyzed using the SPSS software, v. 23. (*SPS*, Bologna, Italy)

#### **3. Results**

#### *3.1. Familial Relationships*

Relations with family members appeared to be felt positively in 54% of patients stating that, being at home, they were closer and linked to each other in a co-working and beloved environment. On the contrary, before the lockdown, family members were less involved; moreover, the use of video calls and socials allowed contact with less frequently seen relatives and increased reciprocal affection and the feeling to be part of the same family. In the control group, a positive evaluation was found only in 30%, although they also stated to have rediscovered human values and lost values.

A negative feeling was reported by 33% of our patients: they described intolerance, impatience, discomfort, distress, constriction, and impairment of contact with close relatives, if not by video calls. In contrast, 60% of the control group described a negative feeling of familial interrelationship because of isolation, uncertainty, fear, difficulties in handling children, and anxiety for older relatives with whom it was hard to communicate.

A small percentage of investigated patients (13%) and 10% of the control group denied significant changes, stating that they were used to this aloneness and isolation.

As a whole, no significant differences were observed in the rate of subjects experiencing positive, negative, or unchanged familial relationships between groups (*X*2(2, *N* = 25) = 1.7, *p* = 0.413).
